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1

Platt, Lisa F., and Kayla S. Bolland. "Relationship partners of transgender individuals." Journal of Social and Personal Relationships 35, no. 9 (May 22, 2017): 1251–72. http://dx.doi.org/10.1177/0265407517709360.

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Relationship partners of transgender-identified individuals have distinctive couple-related experiences that are important to understand. The current qualitative study explored the unique elements of the experiences of those who partner with transgender-identified individuals. A sample of 21 participants who were partnered with a transgender person completed a 1-hr, semi-structured interview. The data yielded five important themes: (1) considerations with physical, sexual, and emotional intimacy; (2) changing sexual orientation labels; (3) safety concerns; (4) marginalization and feelings of isolation; and (5) new appreciation for the gender spectrum. The results show that partners experience considerable change in their lives and relationships as a transgender partner transitions. Implications for future research and how to provide support for this often-overlooked population are provided.
2

Gamarel, Kristi E., Jae M. Sevelius, Torsten B. Neilands, Rachel L. Kaplan, Mallory O. Johnson, Tooru Nemoto, Lynae A. Darbes, and Don Operario. "Couples-based approach to HIV prevention for transgender women and their partners: study protocol for a randomised controlled trial testing the efficacy of the ‘It Takes Two’ intervention." BMJ Open 10, no. 10 (October 2020): e038723. http://dx.doi.org/10.1136/bmjopen-2020-038723.

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IntroductionHIV transmission and acquisition risk among transgender women is particularly high in the context of primary partnerships. This project extends a previous pilot couples-focused HIV intervention programme, which was shown to be feasible, acceptable and promising in reducing sexual risk behaviour among transgender women and their partners. This randomised controlled trial (RCT) tests the efficacy of this culturally sensitive HIV prevention programme for HIV-serodiscordant and HIV-negative seroconcordant transgender women and their partners.Methods and analysisTo finalise the protocol for trial, we used qualitative methods to hone eligibility criteria, refine the intervention and control manuals, and name and brand the intervention (‘It Takes Two’). The RCT investigates the effects of the It Takes Two intervention on Composite Risk for HIV (CR-HIV) among 100 couples. CR-HIV is a binary indicator of couple HIV risk using validated measures of sexual behaviour, pre-exposure prophylaxis use among HIV-negative participants and viral suppression among participants living with HIV. Using a two-arm RCT, we will examine intervention effects on CR-HIV at 12-month follow-up comparing transgender women and their partners randomised to the intervention versus control (HIV prevention information only).Ethics and disseminationThis study has been reviewed and approved by the University of California, San Francisco (19-28624) and the University of Michigan (HUM00147690) Institutional Review Boards. Participants provide informed consent before taking part of the study activities. Results will be published in peer-reviewed journals and presented at scientific conferences. We will make our results available to the community of researchers and general public interested in transgender health to avoid unintentional duplication of research, as well as to others in the health and social services community, including LGBT community-based organisations, AIDS service organisations and other transgender-serving organisations. The full de-identified dataset and codebook will be shared at the University of Michigan Digital Repository.Trial registration numberNCT04067661.
3

Bischof, Gary. "Couple Relationships of Transgender Individuals and their Partners: A 2017 Update." Michigan Family Review 20, no. 1 (September 28, 2017): 37. http://dx.doi.org/10.3998/mfr.4919087.0020.106.

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4

Rutter, Philip A., Nancy N. Leech, Maggie Anderson, and Diana Saunders. "Couples Counseling for a Transgender-Lesbian Couple: Student Counselors’ Comfort and Discomfort with Sexuality Counseling Topics." Journal of GLBT Family Studies 6, no. 1 (February 3, 2010): 68–79. http://dx.doi.org/10.1080/15504280903472816.

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5

Condat, Agnès, Grégor Mamou, Chrystelle Lagrange, Nicolas Mendes, Joy Wielart, Fanny Poirier, François Medjkane, et al. "Transgender fathering: Children’s psychological and family outcomes." PLOS ONE 15, no. 11 (November 19, 2020): e0241214. http://dx.doi.org/10.1371/journal.pone.0241214.

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Medical advances in assisted reproductive technology have created new ways for transgender persons to become parents outside the context of adoption. The limited empirical data does not support the idea that trans-parenthood negatively impacts children’s development. However, the question has led to lively societal debates making the need for evidence-based studies urgent. We aimed to compare cognitive development, mental health, gender identity, quality of life and family dynamics using standardized instruments and experimental protocols in 32 children who were conceived by donor sperm insemination (DSI) in French couples with a cisgender woman and a transgender man, the transition occurring before conception. We constituted two control groups matched for age, gender and family status. We found no significant difference between groups regarding cognitive development, mental health, and gender identity, meaning that neither the transgender fatherhood nor the use of DSI had any impact on these characteristics. The results of the descriptive analysis showed positive psycho-emotional development. Additionally, when we asked raters to differentiate the family drawings of the group of children of trans-fathers from those who were naturally conceived, no rater was able to differentiate the groups above chance levels, meaning that what children expressed through family drawing did not indicate cues related to trans-fatherhood. However, when we assessed mothers and fathers with the Five-Minute Speech Sample, we found that the emotions expressed by transgender fathers were higher than those of cisgender fathers who conceived by sex or by DSI. We conclude that the first empirical data regarding child development in the context of trans-parenthood are reassuring. We believe that this research will also improve transgender couple care and that of their children in a society where access to care remains difficult in this population. However, further research is needed with adolescents and young adults.
6

Zucker, Kenneth J. "Epidemiology of gender dysphoria and transgender identity." Sexual Health 14, no. 5 (2017): 404. http://dx.doi.org/10.1071/sh17067.

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This review provides an update on the epidemiology of gender dysphoria and transgender identity in children, adolescents and adults. Although the prevalence of gender dysphoria, as it is operationalised in the fifth edtion of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), remains a relatively ‘rare’ or ‘uncommon’ diagnosis, there is evidence that it has increased in the past couple of decades, perhaps reflected in the large increase in referral rates to specialised gender identity clinics. In childhood, the sex ratio continues to favour birth-assigned males, but in adolescents, there has been a recent inversion in the sex ratio from one favouring birth-assigned males to one favouring birth-assigned females. In both adolescents and adults, patterns of sexual orientation vary as a function of birth-assigned sex. Recent studies suggest that the prevalence of a self-reported transgender identity in children, adolescents and adults ranges from 0.5 to 1.3%, markedly higher than prevalence rates based on clinic-referred samples of adults. The stability of a self-reported transgender identity or a gender identity that departs from the traditional male–female binary among non-clinic-based populations remains unknown and requires further study.
7

Villela, Lucinéa Marcelino, and Gonzalo Iturregui-Gallardo. "AUDIO DESCRIPTION AND DIVERSITY AWARENESS: FLUTUA MUSIC VIDEO." Trabalhos em Linguística Aplicada 59, no. 2 (August 2020): 1513–30. http://dx.doi.org/10.1590/010318137470211520200702.

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ABSTRACT Brazil has the highest murder rate of transgender people in the world. The paper will focus on a debate of how audio description of some audiovisual products should be used to call the attention to the discrimination and violence suffered by homosexual couples. We have chosen a Brazilian music video called Flutua produced and performed by Johnny Hooker with special participation of the Brazilian singer Liniker, a black trans woman. The clip presents an outstanding visual narrative involving contemporary themes such as gays with disability, gender-fluid and homophobia. During the video a gay deaf couple spends a day having fun with friends in an urban scenario composed by known streets and places of Sao Paulo capital. At the end of the day a member of the group suffered a very violent attack. The audio description of the most relevant scenes, the identities and outfit of the singers, and their movements will be presented having in mind the music as protagonist of Flutua.
8

Cook-Daniels, Loree. "Intimate Partner Violence in Transgender Couples: “Power and Control” in a Specific Cultural Context." Partner Abuse 6, no. 1 (2015): 126–40. http://dx.doi.org/10.1891/1946-6560.6.1.126.

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Applying a “power and control” lens to high-stakes conflicts involving a trans1 person and their intimate partner can both illuminate and distort the true picture of what is going on. This article discusses 6 ways in which discriminatory societal structures and/or cultural beliefs specific to trans people and their families can be wielded as power and control weapons by both trans people and their non-trans partners. These same “abuse tactics” may, however, simply be evidence of a lack of collaborative problem-solving beliefs and skills. The difference between the two is illustrated using common issues likely to be faced by a couple undergoing or contemplating a gender transition. This article ends with specific issues and concerns that should be addressed when safety planning with a trans person or their partner.
9

Ceatha, Nerilee, Paula Mayock, Jim Campbell, Chris Noone, and Kath Browne. "The Power of Recognition: A Qualitative Study of Social Connectedness and Wellbeing through LGBT Sporting, Creative and Social Groups in Ireland." International Journal of Environmental Research and Public Health 16, no. 19 (September 27, 2019): 3636. http://dx.doi.org/10.3390/ijerph16193636.

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The broad research consensus suggesting substantial vulnerabilities among lesbian, gay, bisexual and transgender (LGBT) communities may fail to recognize the protective factors available to these populations. The sparse literature on mental health promotion highlights the importance of understanding strengths-based community approaches that promote LGBT wellbeing. Informed by the Ottawa Charter for Health Promotion, underpinned by Honneth’s Theory of Recognition, this paper outlines the findings of a qualitative Irish study on LGBT social connectedness through a diverse range of sporting, creative and social interests. Ten in-depth interviews were conducted with 11 people (including one couple) who self-identified as lesbian (5), gay (4), bisexual (1) and transgender (1) aged between 22 and 56 years. A university Research Ethics Committee granted approval. The data were transcribed and coded using thematic analysis, enhanced through a memo-writing approach to reflexivity. The theme of ‘connecting’ emphasized the shared nature of activities, with like-minded others through groups established by, and for, LGBT communities. Messages from the study reinforce the central role of LGBT communities in the promotion of mental health and social wellbeing, with important policy and practice implications. This requires the contextualization of the contribution of LGBT communities within understandings of social justice, identity and recognition.
10

Lee, Joseph G. L., Marcella H. Boynton, Bonnie E. Shook-Sa, and Thomas Wimark. "Is Where Same-Sex Couples Live a Valid Measure for Where Single Lesbian, Gay, and Bisexual People Live in Population Health Research? Results from a National Probability Phone Survey, 2017, United States." Annals of LGBTQ Public and Population Health 1, no. 2 (June 1, 2020): 96–114. http://dx.doi.org/10.1891/lgbtq-2019-0009.

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Emerging evidence using the concentration of same-sex couples from the U.S. Census suggests lesbian, gay, bisexual (LGB), and transgender (LGBT; i.e., sexual and gender minority [SGM]) people living as a same-sex couple are concentrated in less healthful neighborhoods. However, it is unclear if findings would be different if based on where LGBT individuals live. Thus, we sought to assess differences in neighborhood, county, and state characteristics between same-sex couples and LGBT individuals to inform population health research and policy interventions on LGBT health inequities. In 2017, we conducted a cross-sectional national, probability survey of LGBT adults in the U.S. and geocoded addresses (N = 407). We linked locations with census tract, county, and state characteristics selected based on health inequities theories. In 2019, we used weighted analysis to calculate descriptive statistics and conducted planned contrasts of location characteristics by both cohabitation status and gender. Many location characteristics were similar by cohabitation status and gender. However, the tract proportion of Black residents and county crime rate were lower for cohabitating than non-cohabitating men. State smoke-free air score was weaker for cohabitating than non-cohabitating women. The use of same-sex couples to determine the geographical clustering of LGBT lives in the U.S. may give a reasonable indication of overall spatial characteristics but can underestimate some important determinants of health. Care should be taken using same-sex couples as a proxy for LGBT concentration when racial segregation is a potential confounder.
11

Brown, Kristina S., Kara Londergan, and Marina Bluvshtein. "And They Lived Happily Ever After: An Intimate Closeness of Systems and Adlerian Theories in the Case of a Transgender Couple." Journal of Individual Psychology 76, no. 1 (2020): 128–40. http://dx.doi.org/10.1353/jip.2020.0023.

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12

Demone, Bradley. "LGBT Rights in Malawi: One Step Back, Two Steps Forward? The Case of R v Steven Monjeza Soko and Tiwonge Chimbalanga Kachepa." Journal of African Law 60, no. 3 (October 2016): 365–87. http://dx.doi.org/10.1017/s0021855316000127.

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AbstractIn late 2009 two Malawians, a man and a transgender woman, united in an engagement ceremony. Police charged both under Malawi's anti-sodomy provisions. The case captured the nation's attention and drew scrutiny from foreign governments and human rights organizations. Several western nations threatened to withdraw aid unless the prosecution was discontinued. Nevertheless, the defendants were convicted and sentenced. Following a visit from the UN secretary general, Malawi's president pardoned the couple, but emphasized that the “two gay boys” had offended Malawi and its people. This article examines this case (R v Soko and Kachepa) and its impact on Malawi's LGBT rights movement. Using Thomas Stoddard's “rule-shifting, culture-shifting” paradigm, it considers the efficacy of international and domestic advocacy efforts and concludes that aid conditionality is, in many ways, counter productive. Conversely, multi-dimensional domestic advocacy is a promising strategy to change the relevant law and public attitudes associated with the Malawian LGBT community.
13

Damsholt, Inger. "The Brudevals, ‘Danishness’ and lived reality." Nordic Journal of Dance 11, no. 1 (June 1, 2020): 16–27. http://dx.doi.org/10.2478/njd-2020-0003.

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AbstractThis article represents part of the author’s ongoing empirical study of the Danish brudevals (bridal waltz) tradition recognized by the means of three characteristic conditions: a specific piece of music by Niels W. Gade, a particular group choreography in which a circle of clapping guests slowly move closer to the newlywed couple and a final section of the ritual in which guests cut the tips of the groom’s socks. The purpose of the article is to highlight how current realisations of the dance reveal the brudevals as a dynamic living tradition and to show the complexity of the political implications it can have when dancing it. Drawing on Sarah Ahmed’s affect theory, the article argues that different negotiations of the brudevals naturalise various understandings of ‘Danishness’. The article argues that an alternative contemporary form of the brudevals, which incorporates a montage of international popular dance and music, produces a version of national identity that underlines the notion of world citizenship as a significant part of being Danish. In realisations of the brudevals danced by same-sex couples, a kind of ‘Danishness’ is produced through affect that naturalises and celebrates Lesbian, gay, bisexual, transgender, queer/questioning, intersex and asexual (LGBTQIA) marriages. Finally, a Turkish-Danish brudevals produces a multiculturalist understanding of ‘Danishness’, which does not conform to a specific national cultural heritage but can encompass several ethnic groups.
14

Blumer, Markie L. C., Mary S. Green, Sarah J. Knowles, and April Williams. "Shedding Light on Thirteen Years of Darkness: Content Analysis of Articles Pertaining to Transgender Issues In Marriage/Couple and Family Therapy Journals." Journal of Marital and Family Therapy 38 (June 2012): 244–56. http://dx.doi.org/10.1111/j.1752-0606.2012.00317.x.

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15

Chetwynd, Ellen M., and Victoria Facelli. "Lactation Support for LGBTQIA+ Families." Journal of Human Lactation 35, no. 2 (April 11, 2019): 244–47. http://dx.doi.org/10.1177/0890334419831269.

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Background: Despite a documented underutilization of healthcare by the LGBTQIA+ community due to fear of mistreatment, reproduction incurs a likely dependence on the medical system. Within breastfeeding medicine, the language used for breastfeeding or chestfeeding has broadened and there is an emphasis on inclusion of all types of gender identities; however, that care can be heavily biased toward the inclusion of all breasts/chests in infant feeding. Research aim: The purpose of this case study was to examine the impact of queer identity on the gestational and postpartum experience of a bisexual woman married to, and parenting with, a transgender man. It draws into perspective the need to practice in accordance with patients’ self-described gender and parenting roles. Results: The parenting roles of this couple were the same as any married, straight, cisgender couple, yet the family identified as queer. The mother in this case experienced low milk production, but the father had had chest reconstructive surgery and started hormones so that they could enter parenthood as the family they had envisioned for themselves. At no point was there any consideration that the father induce milk production for his baby or that chest reconstructive surgery had been mistimed. Their pregnancy support team was supportive of their gender identities and parenting roles, yet they still found themselves orienting and educating the healthcare team throughout their pregnancy and postpartum experience. Conclusions: Caring for the LGBTQIA+ community requires us to recognize our assumptions and act in affirming ways for all parents, regardless of their family constellation.
16

Sullivan-Clarke, Andrea. "Decolonizing “Allyship” for Indian Country: Lessons from #NODAPL." Hypatia 35, no. 1 (December 18, 2019): 178–89. http://dx.doi.org/10.1017/hyp.2019.3.

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AbstractIn 2016, when #NODAPL first appeared in the mainstream media, many nonnative people approached me about how to support the water protectors. This question can be answered in a couple of ways: first, I might address the specific issue (actions that directly support those at Standing Rock), or second, I might respond more generally about how to be an ally to native people. The two responses highlight a current issue in Indian Country: should nonnatives serve as active bystanders—or should they be allies to native peoples? Being an ally has come under scrutiny, especially given its propensity for epistemic injustice. Some philosophers—such as Rachel McKinnon—argue for dismissing the concept altogether, requiring that individuals serve as active bystanders. Although this may be necessary to support individuals in the transgender community, it lacks the resources to fully address the needs of colonized peoples. In this article, I argue for the operationalization of “ally” in Indian Country insofar as it is subject to decolonizing treatment. Although there is a need for both bystanders and allies in Indian Country, the Indigenous people must define the concepts that are intended to serve them.
17

Ningtiyas, Septiana, and Prijono Satyabakti. "The Differences of Condom use Among Transgender to Regular Partner and Clients." Jurnal Berkala Epidemiologi 4, no. 1 (November 11, 2016): 87. http://dx.doi.org/10.20473/jbe.v4i1.2016.87-99.

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ABSTRACTHIV prevalence among transgender in Surabaya based STBP in 2011 has reached 24%. The high prevalence in the transgender group caused by risky sexual behavior that is not consistent in using condoms and changing sex partners. Transgender sex couples not only client, but transgender have a regular partner also called a boyfriend or husband. Program at transgender condom use has not been effective or has not reached the target. Condom use among transgender is determined by sex partners. The study aimed to describe the differences of condom use among transgender to regular partner and clients. This study used cross sectional design research descriptive with qualitative approach. There were 9 informants to accomplish this study by purposive sampling with certain criteria such as transgenders prostitutes who are associated with association of transgender in Surabaya (Perwakos) that were actively doing prostitution, transgender prostitutes who had a regular partner and transgender prostitutes who performed those sexual activities in Surabaya. The variables studied were knowledge, attitudes, perceptions, condom use. Data were analyzed using transcripts of data, data reduction, data display, verification. The results showed that condom use in regular partner lower than the clients. This is caused by the bad attitude and perception, accompanied domination emotional factors. There were no differences of condom use between regular partner with clients. Therefore necessary to motivate transgender Perwakos to always use a condom during sex with regular partner and clients, as well as increased knowledge of HIV-AIDS and the benefits of condoms to regular partner and transgender clients.Keywords: condom use, transgender, HIV-AIDS, regular partner, clients
18

Ningtiyas, Septiana, and Prijono Satyabakti. "The Differences of Condom use Among Transgender to Regular Partner and Clients." Jurnal Berkala Epidemiologi 4, no. 1 (November 11, 2016): 87. http://dx.doi.org/10.20473/jbe.v4i12016.87-99.

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HIV prevalence among transgender in Surabaya based STBP in 2011 has reached 24%. The high prevalence in the transgender group caused by risky sexual behavior that is not consistent in using condoms and changing sex partners. Transgender sex couples not only client, but transgender have a regular partner also called a boyfriend or husband. Program at transgender condom use has not been effective or has not reached the target. Condom use among transgender is determined by sex partners. The study aimed to describe the differences of condom use among transgender to regular partner and clients. This study used cross sectional design research descriptive with qualitative approach. There were 9 informants to accomplish this study by purposive sampling with certain criteria such as transgenders prostitutes who are associated with association of transgender in Surabaya (Perwakos) that were actively doing prostitution, transgender prostitutes who had a regular partner and transgender prostitutes who performed those sexual activities in Surabaya. The variables studied were knowledge, attitudes, perceptions, condom use. Data were analyzed using transcripts of data, data reduction, data display, verification. The results showed that condom use in regular partner lower than the clients. This is caused by the bad attitude and perception, accompanied domination emotional factors. There were no differences of condom use between regular partner with clients. Therefore necessary to motivate transgender Perwakos to always use a condom during sex with regular partner and clients, as well as increased knowledge of HIV-AIDS and the benefits of condoms to regular partner and transgender clients.Keywords: condom use, transgender, HIV-AIDS, regular partner, clients
19

Bishop, Cleo L., Michal Ramalho, Nachiket Nadkarni, Wing May Kong, Christopher F. Higgins, and Nina Krauzewicz. "Role for Centromeric Heterochromatin and PML Nuclear Bodies in the Cellular Response to Foreign DNA." Molecular and Cellular Biology 26, no. 7 (April 1, 2006): 2583–94. http://dx.doi.org/10.1128/mcb.26.7.2583-2594.2006.

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ABSTRACT Nuclear spatial positioning plays an important role in the epigenetic regulation of eukaryotic gene expression. Here we show a role for nuclear spatial positioning in regulating episomal transgenes that are delivered by virus-like particles (VLPs). VLPs mediate the delivery of plasmid DNA (pDNA) to cell nuclei but lack viral factors involved in initiating and regulating transcription. By tracking single fluorescently labeled VLPs, coupled with luciferase reporter gene assays, we found that VLPs transported pDNA to cell nuclei efficiently but transgenes were immediately silenced by the cell. An investigation of the nuclear location of fluorescent VLPs revealed that the pDNAs were positioned next to centromeric heterochromatin. The activation of transcription by providing viral factors or inhibiting histone deacetylase activity resulted in the localization to euchromatin regions. Further, the activation of transcription induced the recruitment of PML nuclear bodies (PML-NBs) to the VLPs. This association did not play a role in regulating transgene expression, but PML protein was necessary for the inhibition of transgene expression with alpha interferon (IFN-α). These results support a model whereby cells can prevent foreign gene expression at two levels: by positioning transgenes next to centromeric heterochromatin or, if that is overcome, via the type I IFN response facilitated by PML-NB recruitment.
20

Sleutels, Frank, and Denise P. Barlow. "Investigation of Elements Sufficient To Imprint the Mouse Air Promoter." Molecular and Cellular Biology 21, no. 15 (August 1, 2001): 5008–17. http://dx.doi.org/10.1128/mcb.21.15.5008-5017.2001.

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ABSTRACT Imprinted maternal-allele-specific expression of the mouse insulin-like growth-factor type 2 receptor (Igf2r) gene depends on a 3.7-kb element named region 2, located in the second intron of the gene. Region 2 carries a maternal-allele-specific methylation imprint and contains an imprinted CpG island promoter (Air) that expresses a noncoding antisense RNA from the paternal inherited allele only. Here, we use transgenes to test the minimal requirements for imprinting of Air and to test if the action of region 2 is restricted to Igf2r. Transgenes up to 9 kb with Air as a single promoter are expressed but not imprinted. When coupled to the Igf2rCpG island promoter on a 44-kb transgene, Air was imprinted in one of three lines. However, Air on a 4.6-kb fragment is also imprinted in 2 of 14 lines when inserted in an intron of an adenine phosphoribosyltransferase (Aprt) transgene, and in one line, the imprinted methylation and expression ofAir have been transferred onto the AprtCpG island promoter. These data suggest that a dual CpG island promoter setting may facilitate Air imprinting as a short transgene and also show that Air can transfer imprinting onto other genes. However, for reliable Air imprinting, elements are necessary that are located outside a 44-kb region spanning the Air-Igf2r promoters.
21

Scott, Jessica, and Liesl Theron. "The promise of heteronormativity: Marriage as a strategy for respectability in South Africa." Sexualities 22, no. 3 (December 7, 2017): 436–51. http://dx.doi.org/10.1177/1363460717713384.

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Considering marriage a primary institution through which norms are transmitted, the authors examine the ways in which entrance into heteronormative respectability is differently available to transgender-cisgender couples and lesbian couples who marry in South Africa. Through qualitative work with transgender-cisgender and lesbian couples, the authors conclude that though marriage through the Marriage Act should speak for itself, admission to heteronormativity requires a labor of doing heterosexuality, conditioned, for the couples represented here, upon a denial of the transgender person’s transgender identity. At the same time, the Civil Union Act, through which same-sex couples access marriage, has been positioned as a ‘different kind of marriage’, though it offers the same legal benefits, protections, and responsibilities available through the Marriage Act. While marriage through the Marriage Act promises entrance into heteronormativity, lesbian couples who marry through the Civil Union Act become engaged in a discursive process of consolidating respectability within the parameters of their marriages.
22

He, Jin, Qing Yang, and Lung-Ji Chang. "Dynamic DNA Methylation and Histone Modifications Contribute to Lentiviral Transgene Silencing in Murine Embryonic Carcinoma Cells." Journal of Virology 79, no. 21 (November 1, 2005): 13497–508. http://dx.doi.org/10.1128/jvi.79.21.13497-13508.2005.

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ABSTRACT Embryonic stem cells are subjected to a dynamic genome regulation during development. Here we report that the ectopic lentiviral transgenes are quickly silenced in murine embryonic carcinoma P19 cells. The silencing was correlated with CpG hypermethylation in the transgene promoter. Using high-resolution sodium bisulfite genome sequencing, we detected distinct DNA methylation kinetics in different proviral regions. DNase I sensitivity and chromatin immunoprecipitation assays revealed condensed chromatin structure and histone code switch during silencing. Longitudinal analysis of nonsilenced and silenced identical single-cell clones revealed that the silencing was coupled with CpG methylation in the promoter, as well as a global histone H3 deacetylation. Interestingly, the primer binding site and the packaging signal region appeared to serve as a DNA methylation initiation center which was rapidly hypermethylated regardless of transgene silencing and chromatin modifications. Analysis of cellular genes 45 to 50 kbp upstream and downstream of the integration site indicated that transcriptional activities of the flanking host genes were not affected. Genetic modifications of stem cells have great therapeutic potentials and our results picture a dynamic embryonic genome response to ectopic transgene integration that may have important implications in the future safety and efficacy modifications of stem cells.
23

Rivera, Denise S. "Care Without Assumption: The Perceptions of Transgender Persons Regarding Their Experiences With Nursing Care." International Journal for Human Caring 23, no. 3 (September 1, 2019): 242–53. http://dx.doi.org/10.20467/1091-5710.23.3.242.

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Transgender persons lead highly marginalized lives coupled with secondary social issues, making it challenging for them to receive respectful quality healthcare. The purpose of this study was to explore the lived experiences of transgender patients, so that nursing curricular changes may be instituted. The narrative inquiry allowed the exploration of patient perceptions with nursing care. Four themes emerged, including marginalization, uninformed nursing, system factors, and nursing role significance. Transgender persons suffer from discrimination and feelings of marginalization as a result of institutional culture, personal bias, and assumption. More research may support curricular and system advances for transgender patients.
24

Malina, Sula. "Unique Causes And Manifestations of Eating Disorders Within Transgender Populations." Columbia Social Work Review 19, no. 1 (May 4, 2021): 138–57. http://dx.doi.org/10.52214/cswr.v19i1.7241.

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Transgender populations are disproportionately impacted by eating disorders and disordered eating behaviors; however, transgender clients lack access to affirming and culturally responsive mental health care and are frequently undiagnosed. In addition, conventional treatment models for eating disorders do not attend to the unique causes and manifestations of eating disorders among transgender people, which include: minority stress and gender trauma; gender dysphoria and lack of access to safe, gender-affirming treatment; safety concerns and the need for passing; cissexism and resulting disempowerment; and pervasive, harmful beauty standards coupled with hyper-scrutiny of trans bodies. This project includes a summary and analysis of the existing literature and data regarding the causes of and current treatment recommendations for eating disorders within transgender populations. It also suggests a social-work-led shift within eating disorder treatment to center the sociopolitical forces which so often lead to such diagnoses.
25

Flores, Andrew R., Christy Mallory, and Kerith J. Conron. "Public attitudes about emergent issues in LGBTQ rights: Conversion therapy and religious refusals." Research & Politics 7, no. 4 (October 2020): 205316802096687. http://dx.doi.org/10.1177/2053168020966874.

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Following legal recognition of marriages for same-sex couples, new topics have emerged in debates over LGBT rights. While numerous studies of public opinion about gay and transgender rights have been examined, some emergent issues remain underexamined. Two prominent issues are conversion therapy and denials of service based on religious beliefs in a variety of settings. These areas of LGBT rights are dynamic, with some states recently banning conversion therapy on minors, the Trump Administration’s guidance on denials of service by health professionals, and some states funding adoption and foster agencies that refuse to provide services to same-sex couples and LGBT adults. In this study, we assess factors associated with public attitudes on these issues. While we find patterns that are consistent with previous studies, we also find inconsistencies when examining the effects of age, race, partisanship, educational attainment, and interpersonal contact. We further find that being a parent moderates the effects of interpersonal contact. Sometimes the moderated contact effects are large and positive but other times contact effects are negative. The contact effect depends on the particular type of contact such as with LGB people, transgender people, or knowing parents who have a transgender child.
26

Sanders, Douglas. "Sex and Gender Diversity in Southeast Asia." Journal of Southeast Asian Human Rights 4, no. 2 (December 7, 2020): 357. http://dx.doi.org/10.19184/jseahr.v4i2.17281.

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The United Nations human rights system has recognized rights of lesbian, gay, bisexual, transgender and intersex individuals (LGBTI), with key decisions in 2011 and 2016. To what extent are the rights of these groupings respected in Southeast Asia? The visibility of LGBTI is low in Southeast Asia and government attitudes vary. Criminal laws, both secular and Sharia, in some jurisdictions, have prohibitions, but active enforcement is rare. Discrimination in employment is prohibited by law in Thailand and in local laws in the Philippines. Change of legal ‘sex’ for transgender individuals is sometimes possible. Legal recognition of same-sex relationships has been proposed in Thailand and the Philippines, but not yet enacted. Marriage has been opened to same-sex couples in neighboring Taiwan. Laws on adoption and surrogacy generally exclude same-sex couples. So-called ‘normalizing surgery’ on intersex babies needs to be deferred to the child’s maturity, to protect their health and rights.
27

Descartes, Laura. "An Exploratory Study of Single and Coupled Lesbian Mothers' Experiences with Social Support." Canadian Journal of Family and Youth / Le Journal Canadien de Famille et de la Jeunesse 12, no. 1 (January 5, 2020): 269–87. http://dx.doi.org/10.29173/cjfy29533.

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This exploratory interview study reveals ten lesbian mothers’ experiences with different forms of social support. Ten lesbian mothers, five single and five who were part of couples, all with young children and living in southern Ontario, discussed their experiences with emotional, instrumental, and informational support from family, friends and neighbours, the LGBTQ (lesbian, gay, bisexual, transgender, queer/questioning) community, support groups, day cares and schools, health care providers, and online and print resources. Most women had largely positive experiences with family and friends but experienced more variability in the other domains. The mothers’ perceptions of potential support sources’ acceptance of diversity and efforts at inclusivity particularly influenced their willingness to access organized forms of support. The single lesbian mothers’ experiences differed from the coupled lesbian mothers’, although there was overlap. Organizations, service providers, and authors providing assistance and information to prospective and current parents are encouraged to continue to increase their awareness of and efforts at including all families.
28

KASIANZUK, MAKSYM, SVIATOSLAV SHEREMET, and OLESIA TROFYMENKO. "Status of same-sex partnerships in Ukraine." Sociology: Theory, Methods, Marketing, stmm 2019 (3) (October 7, 2020): 143–66. http://dx.doi.org/10.15407/sociology2020.03.143.

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The proposed article aims to summarize available quantitative and qualitative data on same-sex partnerships in Ukraine, including data on the presence of children in such partnerships, over the last twenty years (1999–2018). The increasing number of publications on various aspects of the existence of same-sex couples in English demonstrates the relevance of the topic. The information available in Ukraine is the richest in comparison with other post-Soviet countries of the Central and Eastern Europe and Central Asia region. At the same time, LGBT families remain out of the academic community in Ukraine, and the data collected are mostly contained in the so-called "gray literature" (mainly research reports by public organizations), and are not introduced into scientific circulation. It is shown that, depending on the composition of the sample and the definition of same-sex partnership used by the researchers, this percentage most often falls within the range of 16–28% of surveyed homosexual and bisexual men residing in the capital and regional centers of Ukraine. Quantitative information on women partnerships is extremely limited (one survey of a small sample), and there is no quantitative data for the couples, where one or both partners are transgenders. Quantitative information on children in same-sex partnerships is also very limited, and the data in the literature (with all the methodological disadvantages indicated) ranges from 14% to 29% of LGB, which have children, but it is unknown whether these children were raised in same-sex couples. With regard to quality information, the situation is different — a little bit more is known about the status of women and partly transgender partnerships (including the issue of children in such families) than about male couples. Separate data demonstrates a significant similarity in the same-sex partnership structure to the typical heterosexual egalitarian family model (two partners and their children), taking into account more egalitarian marriage roles, lack of formal status, and associated socio-economic risks. Further research (including national level) should be based on a common understanding of what constitutes “same-sex partnership”, what are the characteristics of same-sex partnership (civil, family), what characteristics of civil partnership turn it into a“family”, etc.
29

Nowakowski, Alexandra C. H., Alan Y. Chan, Jordan Forrest Miller, and J. E. Sumerau. "Illness Management in Older Lesbian, Gay, Bisexual, and Transgender Couples: A Review." Gerontology and Geriatric Medicine 5 (January 2019): 233372141882286. http://dx.doi.org/10.1177/2333721418822865.

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More openly sexually and gender diverse people are aging into later life across the world as generational transitions occur. People identifying many different ways beyond cisgender and heterosexual are diverse with respect to many other characteristics and sociopolitical locations across the globe and may thus experience a wide array of health journeys both individually and as partners in intimate relationships. In this review article, we summarize the major contributions of and ongoing gaps in existing studies about such couples’ experiences of chronic disease management in later life. We focus on three key groups of findings from prior research about the health of older sexually and/or gender diverse couples: care practices, unmet needs, and diverse resources. We outline priorities for future research within and across these topic areas and in varied locations, with unique recommendations for scholars in both academic and clinical settings. These recommendations support greater integration of such populations, topics, and needs in existing discourse on aging and late life. Likewise, recommendations from this review illuminate potential best practices for engaging and serving these elders in both academic and applied settings.
30

Dale, Elizabeth J. "Financial Management and Charitable Giving in Gay and Lesbian Households." Nonprofit and Voluntary Sector Quarterly 47, no. 4 (April 11, 2018): 836–55. http://dx.doi.org/10.1177/0899764018768715.

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To date, most charitable giving research assumes that all households are heterosexual and that couples make giving decisions from joint financial resources. This study examines household financial management and charitable decision making among a purposeful sample of 19 gay and lesbian couples. Semistructured joint interviews were conducted and analyzed using grounded theory techniques. The study finds that same-sex couples practice financial management systems that preserve independence (independent and partial-pooling systems), in contrast to different-sex couples, who favor joint management. These systems yield more accounts from which charitable giving can occur. Same-sex couples’ giving does not always follow the household’s financial management structure, and many couples give both jointly and separately. Finally, some same-sex couples use their giving as a way to give lesbian, gay, and bisexual people visibility and recognition as supporters of mainstream (non-LGBT [lesbian, gay, bisexual, and transgender]) organizations. Future research should consider both sexual orientation and financial management practices in understanding charitable behavior.
31

Perosa, Linda M., Sandra L. Perosa, and John Queener. "Assessing Competencies for Counseling Lesbian, Gay, Bisexual, and Transgender Individuals, Couples, and Families." Journal of LGBT Issues in Counseling 2, no. 2 (June 13, 2008): 159–69. http://dx.doi.org/10.1080/15538600802125613.

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32

Carr, Daniel J. J., Lisa Tomanek, Robert H. Silverman, Iain L. Campbell, and Bryan R. G. Williams. "RNA-Dependent Protein Kinase Is Required for Alpha-1 Interferon Transgene-Induced Resistance to Genital Herpes Simplex Virus Type 2." Journal of Virology 79, no. 14 (July 2005): 9341–45. http://dx.doi.org/10.1128/jvi.79.14.9341-9345.2005.

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ABSTRACT We investigated the mechanism of resistance to genital herpes simplex virus type 2 (HSV-2) infection in mice transfected with the murine alpha-1 interferon (IFN-α1) transgene. In situ transfection of mice with the IFN-α1 transgene resulted in an elevation in an IFN-responsive gene, RNA-dependent protein kinase (PKR), but not 2′,5′-oligoadenylate synthetases (OAS), in vaginal tissue. Coupled with the finding that mice lacking a functional PKR pathway were no longer resistant to genital HSV-2 infection following transfection with the IFN-α1 transgene in comparison to wild-type mice or mice lacking a functional OAS pathway, these results suggest that PKR is the dominant antiviral pathway activated by the IFN-α1 transgene.
33

Samons, Sandra L. "Can this marriage be saved? Addressing male-to-female transgender issues in couples therapy." Sexual and Relationship Therapy 24, no. 2 (May 2009): 152–62. http://dx.doi.org/10.1080/14681990903002748.

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34

Roth, K. A., S. M. Cohn, D. C. Rubin, J. F. Trahair, M. R. Neutra, and J. I. Gordon. "Regulation of gene expression in gastric epithelial cell populations of fetal, neonatal, and adult transgenic mice." American Journal of Physiology-Gastrointestinal and Liver Physiology 263, no. 2 (August 1, 1992): G186—G197. http://dx.doi.org/10.1152/ajpgi.1992.263.2.g186.

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Little is known about lineage relationships and differentiation programs of various epithelial cells present in mouse gastric units. We have previously used rat liver fatty acid binding protein/human growth hormone (L-FABP/hGH) transgenes to define epithelial cell lineages relationships in the small intestine of fetal and adult mice and to examine regulation of their terminal differentiation programs along the crypt-to-villus and duodenal-to-ileal axes. We have now used these transgenes to explore similar issues in the stomach. Immunocytochemical studies of fetal and adult transgenic L-FABP/hGH animals and their normal littermates revealed that the intact endogenous mouse L-FABP gene (Fabpl) is not expressed in gastric epithelium. Nucleotides-596 to +21 of the rat L-FABP gene direct "inappropriate" expression of hGH in the gastric epithelium as early as fetal day 15. From 1 to 13 mo, L-FABP-596 to +21/hGH expression occurs only in surface mucous cells of zymogenic and mucous gastric units; the reporter is not detectable in the enteroendocrine, parietal and chief cell populations of zymogenic glands. Electron microscopic immunocytochemistry revealed that hGH is directed to apical secretory granules in surface and pit mucous cells expressing the transgene. hGH levels vary widely among surface mucous cells both within single pits and between gastric units in a given animal. The heterogeneity noted in reporter expression suggests that there are marked differences in the regulatory environments of individual cells of a single type within a given gastric unit. This raises the possibility that cell differentiation programs in the stomach may not be as tightly coupled to cellular translocation as in the small intestine. Finally, the lack of expression of L-FABP-596 to +21/hGH in gastrin- and serotonin-immunoreactive cells of the stomach contrasts with its efficient expression in comparable cell types located in the duodenum; providing a model system for examining differential regulation of gene expression in terminally differentiated cell types represented in both gastric and intestinal epithelium.
35

Kidd, Jeremy D., and Tarynn M. Witten. "Understanding Spirituality and Religiosity in the Transgender Community: Implications for Aging." Journal of Religion, Spirituality & Aging 20, no. 1-2 (March 27, 2008): 29–62. http://dx.doi.org/10.1080/15528030801922004.

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36

Arístegui, Inés, Alejandro Castro Solano, and Abraham P. Buunk. "Mate preferences in Argentinean transgender people: An evolutionary perspective." Personal Relationships 25, no. 3 (August 2018): 330–50. http://dx.doi.org/10.1111/pere.12247.

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37

Zhang, Jing, Osamu Yamada, Takashi Sakamoto, Hiroshi Yoshida, Hiromasa Araki, and Kunitada Shimotohno. "Exploiting cis-Acting Replication Elements To Direct Hepatitis C Virus-Dependent Transgene Expression." Journal of Virology 79, no. 10 (May 15, 2005): 5923–32. http://dx.doi.org/10.1128/jvi.79.10.5923-5932.2005.

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ABSTRACT We describe here a novel targeting gene therapy strategy to direct gene expression responsive to hepatitis C virus (HCV). The goal was approached by engineering a construct containing the antisense sequence of the transgene and internal ribosome entry site of encephalomyocarditis virus flanked by 5′- and 3′-end sequences of HCV cDNA that contain cis-acting replication elements. Thus, expression of the transgene is only promoted when the minus-strand RNA has been synthesized by the functional replication machinery present in infected cells. Reporter assay and strand-specific reverse transcription-PCR showed selective transgene expression in Huh-7 cells harboring an autonomously replicating HCV subgenome but remaining silent in uninfected cells. Furthermore, using the cytosine deaminase suicide gene as a transgene coupled with recombinant adenovirus delivery, we demonstrated that cytosine deaminase was specifically expressed in replicon cells, resulting in marked chemosensitization of replicon cells to the cytotoxic effects of flucytosine. This new targeting strategy could be extended to other single-stranded RNA viruses encoding the unique RNA-dependent RNA polymerase that has no parallel in mammalian cells.
38

Grooms, Jevay. "No Home and No Acceptance: Exploring the Intersectionality of Sexual/Gender Identities (LGBTQ) and Race in the Foster Care System." Review of Black Political Economy 47, no. 2 (March 11, 2020): 177–93. http://dx.doi.org/10.1177/0034644620911381.

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Black youth have been overrepresented in the U.S. foster care system for decades. This, coupled with disparities in treatment and outcomes, has forced all child welfare agencies to take note and influenced policy change, at the federal level. Recently, literature has begun to bring to light the existence of a substantial LGBTQ (lesbian, gay, bisexual, transgender, and queer) foster youth population which is overrepresented and underserved. This article offers a comprehensive look at the LGBTQ foster youth population, its vulnerabilities, and its distinct needs. It further contributes to the existing body of literature by exploring the intersectionality of foster youth who identify as Black and LGBTQ.
39

Yamaguti-Hayakawa, Gabriela G., and Margareth C. Ozelo. "Gene Therapy: Paving New Roads in the Treatment of Hemophilia." Seminars in Thrombosis and Hemostasis 45, no. 07 (May 16, 2019): 743–50. http://dx.doi.org/10.1055/s-0039-1688445.

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AbstractHemophilia is a monogenic disease with robust clinicolaboratory correlations of severity. These attributes coupled with the availability of experimental animal models have made it an attractive model for gene therapy. The road from animal models to human clinical studies has heralded significant successes, but major issues concerning a previous immunity against adeno-associated virus and transgene optimization remain to be fully resolved. Despite significant advances in gene therapy application, many questions remain pertaining to its use in specific populations such as those with factor inhibitors, those with underlying liver disease, and pediatric patients. Here, the authors provide an update on viral vector and transgene improvements, review the results of recently published gene therapy clinical trials for hemophilia, and discuss the main challenges facing investigators in the field.
40

Teng, Peter I., Maria R. Dichiara, László G. Kömüves, Keith Abe, Thomas Quertermous, and James N. Topper. "Inducible and selective transgene expression in murine vascular endothelium." Physiological Genomics 11, no. 2 (October 29, 2002): 99–107. http://dx.doi.org/10.1152/physiolgenomics.00059.2002.

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We have developed a system utilizing the murine Tie2 promoter/enhancer coupled with the “tetracycline-on” regulatory elements to create a model that allows regulated and selective expression of a β-galactosidase (βGal) reporter transgene in the adult murine vascular endothelium. Two independent lines of viable and fertile mice were characterized, and they exhibit minimal βGal expression under basal conditions. In response to exogenous doxycycline (Dox), selective expression of βGal was demonstrated in the vascular endothelium of all tissues examined. En face analyses of the aorta and its principle branches indicate that the vast majority of lumenal endothelial cells express the transgene. Inducible βGal expression also extends to the endocardium and the microvasculature of all organs. There is no evidence of specific transgene expression in nonendothelial cell types. Induction of the βGal was effectively achieved after 3 days of oral Dox treatment and persisted for over 3 mo with continuous administration. This model can now be widely applied to study the role of specific genes in the phenotype of adult murine vasculature.
41

Daniels, G. A., M. Chan, C. C. Wu, R. Tawatao, D. Messmer, B. Eftimie, H. Cottam, and D. Carson. "Covalent coupling of a novel TLR7 agonist to antigen elicits an effective immune response in a murine melanoma tumor model." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 3019. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.3019.

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3019 Background: Toll-like receptor (TLR) signaling triggers innate immune stimulation capable of generating an adaptive immune response under appropriate conditions. TLR agonists have shown efficacy in preclinical and clinical cancer therapies. However, one limitation to this approach has been the use of TLR agonists delivered at distances away from the target (ie-subcutaneous injections for general immune stimulation) or the inability to effectively couple antigen with adjuvant. Methods: We have synthesized a novel TLR7 agonist capable of covalent coupling to primary amines under physiologic conditions. In vitro activity of adjuvant alone or antigen-adjuvant complexes were tested for innate immune activation by utilizing bone marrow-derived murine or peripheral blood mononuclear cell-derived dendritic cells (DC) with respect to DC maturation and cytokine secretion (IL12, IL6, TGFbeta and IFNgamma). Immunocompetent syngeneic C57/b6 mice were prophylactically vaccinated with intradermal with either antigen, antigen mixed with adjuvant or antigen- adjuvant coupled complexes and challenged with B16 melanoma tumor cells expressing the cOVA transgene. Results: The effective concentration (EC50) for each compound generally followed a bell shaped distribution with higher doses being inhibitory. Maximal stimulation occurred between 10 and 1000nM. Coupled adjuvant molecules retained activity with generally lower EC50 values. Coupling 1V199 to chicken ovalbumin nearly doubled median survival from 22 to 35 days following subcutaneous tumor challenge compared with chicken ovalbumin alone. Conclusions: Covalent linkage of a TLR7 agonist to antigen stimulates DC cytokine production and protects mice from tumor challenge. Use of a soluble TLR7 agonist which retains its immune stimulating properties following coupling to antigen under physiologic conditions may be useful in the development of an in situ vaccine in solid tumor therapy. No significant financial relationships to disclose.
42

Reisner, Sari L., David Menino, Kingsley Leung, and Kristi E. Gamarel. "“Unspoken Agreements”: Perceived Acceptability of Couples HIV Testing and Counseling (CHTC) Among Cisgender Men with Transgender Women Partners." AIDS and Behavior 23, no. 2 (June 23, 2018): 366–74. http://dx.doi.org/10.1007/s10461-018-2198-y.

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43

Cooper, Robert L., Mohammad Tabatabai, Paul D. Juarez, Aramandla Ramesh, Matthew C. Morris, Katherine Y. Brown, Thomas A. Arcury, Marybeth Shinn, Leandro A. Mena, and Patricia-Matthews Juarez. "Pre-Exposure Prophylaxis Training among Medical Schools in the United States." Journal of Primary Care & Community Health 12 (January 2021): 215013272110287. http://dx.doi.org/10.1177/21501327211028713.

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Pre-Exposure Prophylaxis (PrEP) has been shown to be an effective method of HIV prevention for men who have sex with-men (MSM) and -transgender women (MSTGWs), serodiscordant couples, and injection drug users; however fewer than 50 000 individuals currently take this regimen. Knowledge of PrEP is low among healthcare providers and much of this lack of knowledge stems from the lack or exposure to PrEP in medical school. We conducted a cross sectional survey of medical schools in the United States to assess the degree to which PrEP for HIV prevention is taught. The survey consisted Likert scale questions assessing how well the students were prepared to perform each skill associated with PrEP delivery, as well as how PrEP education was delivered to students. We contacted 141 medical schools and 71 responded to the survey (50.4%). PrEP education was only reported to be offered at 38% of schools, and only 15.4% reported specific training for Lesbian, Gay, Bisexual, and Transgender (LGBT) patients. The most common delivery methods of PrEP content were didactic sessions with 11 schools reporting this method followed by problem-based learning, direct patient contact, workshops, and small group discussions. Students were more prepared to provide PrEP to MSM compared to other high-risk patients. Few medical schools are preparing their students to prescribe PrEP upon graduation. Further, there is a need to increase the number of direct patient contacts or simulations for students to be better prepared.
44

Operario, Don, Kristi E. Gamarel, Mariko Iwamoto, Sachico Suzuki, Sabrina Suico, Lynae Darbes, and Tooru Nemoto. "Couples-Focused Prevention Program to Reduce HIV Risk Among Transgender Women and Their Primary Male Partners: Feasibility and Promise of the Couples HIV Intervention Program." AIDS and Behavior 21, no. 8 (June 22, 2016): 2452–63. http://dx.doi.org/10.1007/s10461-016-1462-2.

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45

Mingozzi, Federico, Nicole C. Hasbrouck, Etiena Basner-Tschakarjan, Shyrie A. Edmonson, Daniel J. Hui, Denise E. Sabatino, Shangzhen Zhou, et al. "Modulation of tolerance to the transgene product in a nonhuman primate model of AAV-mediated gene transfer to liver." Blood 110, no. 7 (October 1, 2007): 2334–41. http://dx.doi.org/10.1182/blood-2007-03-080093.

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Adeno-associated virus (AAV)–mediated gene transfer of factor IX (F.IX) to the liver results in long-term expression of transgene in experimental animals, but only short-term expression in humans. Loss of F.IX expression is likely due to a cytotoxic immune response to the AAV capsid, which results in clearance of transduced hepatocytes. We used a nonhuman primate model to assess the safety of AAV gene transfer coupled with an anti–T-cell regimen designed to block this immune response. Administration of a 3-drug regimen consisting of mycophenolate mofetil (MMF), sirolimus, and the anti–IL-2 receptor antibody daclizumab consistently resulted in formation of inhibitory antibodies to human F.IX following hepatic artery administration of an AAV-hF.IX vector, whereas a 2-drug regimen consisting only of MMF and sirolimus did not. Administration of daclizumab was accompanied by a dramatic drop in the population of CD4+CD25+FoxP3+ regulatory T cells (Tregs). We conclude that choice of immunosuppression (IS) regimen can modulate immune responses to the transgene product upon hepatic gene transfer in subjects not fully tolerant; and that induction of transgene tolerance may depend on a population of antigen-specific Tregs.
46

Andrews, Sarah F., Qingzhao Zhang, Samuel Lim, Lie Li, Jane-Hwei Lee, Nai-Ying Zheng, Min Huang, et al. "Global analysis of B cell selection using an immunoglobulin light chain–mediated model of autoreactivity." Journal of Experimental Medicine 210, no. 1 (December 24, 2012): 125–42. http://dx.doi.org/10.1084/jem.20120525.

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The important subtleties of B cell tolerance are best understood in a diverse immunoglobulin (Ig) repertoire context encoding a full spectrum of autoreactivity. To achieve this, we used mice expressing Igκ transgenes that confer varying degrees of autoreactivity within a diverse heavy chain (HC) repertoire. These transgenes, coupled with a biomarker to identify receptor-edited cells and combined with expression cloning of B cell receptors, allowed us to analyze tolerance throughout B cell development. We found that both the nature of the autoantigen and the Ig HC versus light chain (LC) contribution to autoreactivity dictate the developmental stage and mechanism of tolerance. Furthermore, although selection begins in the bone marrow, over one third of primary tolerance occurs in the periphery at the late transitional developmental stage. Notably, we demonstrate that the LC has profound effects on tolerance and can lead to exacerbated autoantibody production.
47

Tsai, Jo C., Lixin Liu, Jie Zhang, Katherine C. Spokes, James N. Topper, and William C. Aird. "Epidermal growth factor induces Egr-1 promoter activity in hepatocytes in vitro and in vivo." American Journal of Physiology-Gastrointestinal and Liver Physiology 281, no. 5 (November 1, 2001): G1271—G1278. http://dx.doi.org/10.1152/ajpgi.2001.281.5.g1271.

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Early growth response-1 (Egr-1) is a transcription factor that couples short-term changes in the extracellular milieu to long-term changes in gene expression. Under in vitro conditions, the Egr-1 gene has been shown to respond to many extracellular signals. In most cases, these findings have not been extended to the in vivo setting. The goal of the present study was to explore the role of epidermal growth factor (EGF) in mediating Egr-1 expression in hepatocytes under both in vitro and in vivo conditions. In HepG2 cells, Egr-1 protein and mRNA were upregulated in the presence of EGF. In stable transfections of HepG2 cells, a 1,200-bp Egr-1 promoter contained information for EGF response via a protein kinase C-independent, mitogen-activated protein kinase-dependent signaling pathway. A promoter region containing the two most proximal serum response elements was sufficient to transduce the EGF signal. In transgenic mice that carry the Egr-1 promoter coupled to the LacZ reporter gene, systemic delivery of EGF by intraperitoneal injection resulted in an induction of the endogenous Egr-1 gene and the Egr-1- lacZ transgene in hepatocytes. Together, these results suggest that the 1,200-bp promoter contains information for EGF response in hepatocytes both in vitro and in intact animals.
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Gundersen, K., J. R. Sanes, and J. P. Merlie. "Neural regulation of muscle acetylcholine receptor epsilon- and alpha-subunit gene promoters in transgenic mice." Journal of Cell Biology 123, no. 6 (December 15, 1993): 1535–44. http://dx.doi.org/10.1083/jcb.123.6.1535.

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The effects of denervation were investigated in mice with transgenes containing promoter elements from the muscle acetylcholine receptor epsilon- and alpha-subunit genes. The promoter sequences were coupled to a nuclear localization signal-beta-galactosidase fusion gene (nlacZ) as a reporter. While many postsynaptic specializations form in the embryo, expression of the epsilon subunit is induced during the first two postnatal weeks. When muscles were denervated at birth, before the onset of epsilon expression, epsilon nlacZ still appeared at the former synaptic sites on schedule. This result suggests that the nerve leaves a localized "trace" in the muscle that can continue to regulate transcription. An additional finding was that epsilon nlacZ expression was much stronger in denervated than in intact muscles. This suggests that the epsilon promoter is similar to the other subunits in containing elements that are activated on cessation of neural activity. However, even after denervation, epsilon nlacZ expression was always confined to the synaptic region whereas alpha nlacZ expression increased in nuclei along the entire length of the fiber. This suggests that while the epsilon gene is similar in its activity dependence to other subunit genes, it is unique in that local nerve-derived signals are essential for its expression. Consequently, inactivity enhances epsilon expression only in synaptic nuclei where such signals are present, but enhances expression throughout the muscle fiber. Truncations and an internal deletion of the epsilon promoter indicate that cis-elements essential for the response to synaptic signals are contained within 280 bp of the transcription start site. In contrast to these results in young animals, denervation in older animals leads to an unexpected reduction in nlacZ activity. However, mRNA measurements indicated that transgene expression was increased in these animals. This discordance between nlacZ mRNA and enzyme activity, demonstrates a previously unknown limitation of nlacZ as a reporter gene in transgenic animals.
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Porter, Kristen E., Corina R. Ronneberg, and Tarynn M. Witten. "Religious Affiliation and Successful Aging Among Transgender Older Adults: Findings From the Trans MetLife Survey." Journal of Religion, Spirituality & Aging 25, no. 2 (April 2013): 112–38. http://dx.doi.org/10.1080/15528030.2012.739988.

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50

Provasi, Elena, Oscar Muniz Pello, Zulma Magnani, Jurgen Kuball, Angelo Lombardo, Attilio Bondanza, Philip D. Gregory, et al. "T Cell Receptor Gene Transfer into Naive and Central Memory Lymphocytes by Lentiviral Vectors for a Safe and Effective Adoptive Immune Therapy of Leukemia." Blood 112, no. 11 (November 16, 2008): 3529. http://dx.doi.org/10.1182/blood.v112.11.3529.3529.

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Abstract The potency of cellular adoptive immunotherapy against cancer has been revealed by persistent and complete clinical responses obtained with allogeneic hemopoietic cell transplantation (allo-HSCT) followed by the adoptive transfer of donor T lymphocytes and by initial clinical responses observed with the adoptive transfer of tumor specific cytotoxic T lymphocytes (CTLs) in cancer patients. Major hurdles limiting adoptive T cell therapy relate to toxicity (i.e. graft-versus-host disease-GvHD in allo-HSCT) and efficacy (i.e. difficulty in expanding rare, high-avidity tumor-specific CTLs in conditions that can preserve their function and prevent exhaustion). The transfer of the T cell receptor (TCR) from high-avidity tumor-specific CTLs to polyclonal lymphocytes may overcome these difficulties, but is still limited by low and transient transgene expression, unpredictable pairing of the exogenous and endogenous TCR chains and poor survival and expansion potential of gene-modified effector lymphocytes. To overcome these limitations, we cloned genes encoding a high-avidity TCR specific for an HLA-A2-restricted peptide from the oncogenic Wilms tumor antigen 1 (WT1126-135), in a third generation lentiviral vector under the control of a bi-directional PGK or a bi-directional EF1α promoter. To increase TCR expression and facilitate appropriate TCR pairing, we used a codon-optimized TCR, modified with point mutations to introduce cysteines into the constant regions of the α and 7β chains. Human T lymphocytes were efficiently transduced by both vectors, following activation with anti-CD3 and anti-CD28 antibody-conjugated beads (bCD3/CD28) and culture with low doses of IL-7/IL-15. However, the PGK promoter was superior to EF1α in sustaining stochiometric expression of WT1-specific TCR chains, at levels appropriate for efficient HLA-A2/WT1 pentamer binding (16%), for up to 50 days, in the absence of further T cell stimulation. Additionally, we observed that a phenotype consistent with early (naïve and central memory) T cell differentiation (CD45RA−/+CD62L+, CD28+CD27+, IL7Ra+, IL-2+ γIFN±) was preserved in TCR-modified lymphocytes generated in these culture conditions. Sorted naïve (CD45RA+/CD62L+) and central memory (CD45RA−/CD62L+) lymphocytes were efficiently transduced by TCR-LV and maintained the original T cell phenotype. Accordingly, TCR-modified lymphocytes showed excellent survival and expansion capacity, and, upon antigenic stimulation mediated high WT1-specific γIFN production and cytotoxic activity. To improve the safety of the strategy, we attempted sitespecific integration of transgenes using of the ZFN technology. Adenoviral transfer of a set of ZFN specific for the putative safe-harbor locus CCR5 coupled with integrase defective lentiviral vectors carrying the donor DNA flanked transgene, enables efficient site-specific integration in human lymphocytes resulting in stable transgene expression. Analyses of sorted gene-modified cells is currently ongoing. Site-specific integration of an optimized, leukemia-specific TCR into both naïve and central memory lymphocytes may represent an effective method for the generation of robust engineered tumor-specific CTLs.

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